Oral care compositions

ABSTRACT

The various aspects presented herein relate to oral care compositions comprising: a) a bioactive component in an amount from 0.01 to 10 wt % of the oral care composition; b) a non-ionic surfactant comprising (i) a surfactant selected from the group consisting of: poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymers, poly(oxyethylene)-modified hydrogenated castor oils, and poly(oxyethylene)-modified fatty acid monoesters of sorbitan, and (ii) a surfactant selected from the group consisting of polyol esters and sugar esters; c) at least one orally acceptable solvent; and optionally, d) a C2-C4 monohydric alcohol, wherein the ratio of the surfactant selected from the group consisting of: poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymers, poly(oxyethylene)-modified hydrogenated castor oils, and poly(oxyethylene)-modified fatty acid monoesters of sorbitan to the surfactant selected from the group consisting of polyol esters and sugar esters is from 1:10 to 10:1; and wherein the ratio of the non-ionic surfactant to the bioactive component is from 0.5 to 3.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims priority to International PatentApplication Serial No. PCT/CN2017/117398, filed on Dec. 20, 2017, theentire contents of which is hereby incorporated by reference in itsentirety.

FIELD OF THE INVENTION

The various aspects presented herein relate to non-alcoholic orslightly-alcoholic oral care compositions, and their use thereof.

BACKGROUND

Oral care preparations, such as, for example, mouthwashes or mouthrinses are developed to clean and refresh the oral cavity or oralsurface by inhibiting or killing the microorganisms that cause malodor,dental caries, tooth decay, gum diseases, gingivitis, and periodontaldisorders. The effectiveness of an oral care composition may be based onits ability to deliver the active ingredient(s) contained therein, tokill the targeted microorganisms.

Conventional oral care compositions typically contain relatively highlevels of C₂-C₄ monohydric alcohol content, ranging from, for example,10% to about 30% v/v of ethyl alcohol. The C₂-C₄ monohydric alcohol maybe employed as a disinfectant or solvent for the added excipients suchas astringents, fluorides, colors, flavors, and the like. Further, thehigher quantity of C₂-C₄ monohydric alcohol is usually employed toprovide a disinfection role since lower amounts are adequate to dissolvethe various ingredients of the oral care composition into solution. TheC₂-C₄ monohydric alcohol may also offer a preservative function for theoral care composition during storage, and may enhance the organolepticor aesthetic properties of an essential oil within the oral carecomposition.

The use of C₂-C₄ monohydric alcohols may be problematic from an overallhealth perspective in part, due to several reasons, including, but notlimited to: (i) the contraindication of C₂-C₄ monohydric alcohol forhealth and safety related reasons; (ii) abuse of alcohol-containing oralcare compositions; (iii) irritation of the protective layers of themouth and throat; or (iv) dry mouth.

However, reducing the amount of C₂-C₄ monohydric alcohol in oral carecompositions is problematic. Lowering the C₂-C₄ monohydric alcoholcontent results in decreased solubility of active ingredients andthereby lesser antimicrobial efficacy of the oral care composition withregard to bad breath, plaque gum disease and the like. Moreover, the useof surfactants to solubilize active ingredients in alcohol-free oralcare compositions may also reduce the antimicrobial efficacy of thecomposition and may cause unpleasant tastes or off-notes in the oralcare compositions.

Consequently, there is a substantial need for the development of anon-alcoholic oral care composition with acceptable off-taste, and whichhas effective antimicrobial efficacy with respect to prevention orreduction of bad breath, the killing of oral bacteria or elimination orreduction of plaque.

SUMMARY

One aspect presented herein, provides an oral care composition,comprising:

-   -   a) a bioactive component in an amount from 0.01 to 10 wt % of        the oral care composition;    -   b) a non-ionic surfactant comprising (i) a surfactant selected        from the group consisting of:        poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block        copolymers, poly(oxyethylene)-modified hydrogenated castor oils,        and poly(oxyethylene)-modified fatty acid monoesters of        sorbitan, and (ii) a surfactant selected from the group        consisting of polyol esters and sugar esters;    -   c) at least one orally acceptable solvent; and optionally,    -   d) a C₂-C₄ monohydric alcohol,        -   wherein the ratio of the surfactant selected from the group            consisting of:            poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block            copolymers, poly(oxyethylene)-modified hydrogenated castor            oils, and poly(oxyethylene)-modified fatty acid monoesters            of sorbitan to the surfactant selected from the group            consisting of polyol esters and sugar esters is from 1:10 to            10:1; and        -   wherein the ratio of the non-ionic surfactant to the            bioactive component is from 0.5 to 3.

In one aspect, the oral care composition further comprises a flavor oil.

In one aspect, the amount of the C₂-C₄ monohydric alcohol is from 0 to10 wt % of the oral care composition.

In one aspect, the amount of the C₂-C₄ monohydric alcohol is from 0 to 5wt % of the oral care composition.

In one aspect, the oral care composition does not comprise the C₂-C₄monohydric alcohol.

In one aspect, thepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymeris the hydrophilic non-ionic surfactant sold under the tradenamePoloxamer 407, comprising a triblock copolymer consisting of a centralhydrophobic block of polypropylene glycol flanked by two hydrophilicblocks of polyethylene glycol (PEG).

In one aspect, the poly(oxyethylene)-modified fatty acid monoester ofsorbitan is Tween 80.

In one aspect, the poly(oxyethylene)-modified fatty acid monoester ofsorbitan is Tween 20.

In one aspect, the sugar ester is selected from the group consisting of:sucrose laurate, sucrose monolaurate, sucrose palmitate, sucrosemonopalmitate, and combinations thereof.

In one aspect, the sugar ester is a sucrose ester. In an alternateaspect, the sugar ester is a fructose ester.

In one aspect, the polyol ester is a glycerol ester.

In one aspect, the polyol ester is monolauric acid decaglycerin ester.

In one aspect, the ratio of the surfactant selected from the groupconsisting of: poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene)block copolymers, poly(oxyethylene)-modified hydrogenated castor oils,and poly(oxyethylene)-modified fatty acid monoesters of sorbitan to thesurfactant selected from the group consisting of polyol esters and sugaresters is from 1:5 to 5:1.

In one aspect, the ratio of the surfactant selected from the groupconsisting of: poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene)block copolymers, poly(oxyethylene)-modified hydrogenated castor oils,and poly(oxyethylene)-modified fatty acid monoesters of sorbitan to thesurfactant selected from the group consisting of polyol esters and sugaresters is from 1:3 to 3:1.

In one aspect, the orally acceptable solvent is selected from the groupconsisting of: water, polyol, sugar alcohols, a C₁₋₆ linear or branchedalkyl lactate, triacetine, triethylcitrate, benzylic alcohol, andcombinations thereof.

In one aspect, the polyol is selected from the group consisting of:polyhydric alcohols, polyalkylene glycols, polyhydric alcohol esters,polyhydric alcohol ethers, and combinations thereof.

In one aspect, the polyhydric alcohol is selected from the groupconsisting of: glycerol, butylene glycol, hexylene glycol,1,3-propanediol, propylene glycol, and combinations thereof.

In one aspect, the polyhydric alcohol is propylene glycol.

In one aspect, the polyhydric alcohol ester and polyhydric alcohol etherare selected from the group consisting of: dipropylene glycol,ethoxydiglycol, and combinations thereof.

In one aspect, the polyalkylene glycol is selected from the groupconsisting of: polyethylene glycol, polypropylene glycol, andcombinations thereof.

In one aspect, the sugar alcohol is selected from the group consistingof: xylitol, sorbitol, mannitol, maltitol, inositol, allitol, altritol,dulcitol, galactitol, glucitol, hexitol, iditol, pentitol, ribitol,erythritol and mixtures thereof.

In one aspect, the sugar alcohol is selected from the group consistingof sorbitol and xylitol or mixtures thereof.

In one aspect, the C₁₋₆ linear or branched alkyl lactate is ethyllactate.

One aspect presented herein provides a method for treating plaque,gingivitis or gum disease in a subject in need thereof, comprising thestep of applying to the tissues of the oral cavity of the subject, anamount of the composition according to the aspects presented hereineffective to reduce symptoms associated with plaque, gingivitis or gumdisease.

DETAILED DESCRIPTION

In the following description, reference is made to specific embodimentswhich may be practiced, which is shown by way of illustration. Theseembodiments are described in detail to enable those skilled in the artto practice the invention described herein, and it is to be understoodthat other embodiments may be utilized and that logical changes may bemade without departing from the scope of the aspects presented herein.The following description of example embodiments is, therefore, not tobe taken in a limited sense, and the scope of the various aspectspresented herein is defined by the appended claims.

The Abstract is provided to comply with 37 C.F.R. § 1.72(b) to allow thereader to quickly ascertain the nature and gist of the technicaldisclosure. The Abstract is submitted with the understanding that itwill not be used to interpret or limit the scope or meaning of theclaims.

Without intending to be limited to any particular theory, the solubilityof essential oils in alcohol-free oral care compositions is limited, dueto the low solubility of the essential oils in water. The low solubilityof the essential oils may lead to an undesirable cloudy oral carecomposition. One solution to this problem is to form micro-emulsions ofthe essential oils, resulting in transparent or translucent oral carecompositions. High amounts of surfactants are usually required to formmicro-emulsions of essential oils in typical alcohol-free oral carecompositions. However, the use of high amounts of surfactants isundesirable, as it reduces the antimicrobial efficacy of the oral carecomposition, and may cause unpleasant taste or off-notes.

The present disclosure provides personal care products intended for useon the oral cavity. In some aspects, the present disclosure providestransparent or translucent alcohol-free or slightly alcoholic oral carecompositions which contain low amounts of surfactants and have highantimicrobial efficacy, having acceptable off-taste and organolepticproperties.

In some aspects, the oral care compositions presented comprisecombinations of non-ionic surfactant or mixtures thereof that contain apolyoxyethylene (POE) group and have a hydrophilic-lipophilic balance(HLB) greater than or equal to 12, alternatively greater than or equalto 15, and another non-ionic surfactant or mixtures thereof chosen fromthe group of polyol esters and sugar esters.

Without intending to be limited to any particular theory, the solubilityof oils can be enhanced by combining surfactants with differenthydrophobicity. In selecting the surfactant for such systems, thesurfactant's hydrophilic-lipophilic balance (HLB) is traditionally isconsidered. The HLB scale is based on the relative percentage ofhydrophilic to lipophilic groups in the surfactant molecule. Forexample, an Oil-in-Water (O/W) emulsion would require a high HLB value(e.g., 10-18) to solubilize the molecules in water. The HLB scale byitself, however, fails to indicate whether a specific surfactant will beeffective as a solubilization agent for active ingredients in acolloidal system, where other compounds, e.g., alcohol, salt andtemperature usually affect the balance of the system. In suchsituations, where the colloidal dispersion system includes activeingredients, the balance of the system should be considered to reachhigh oil solubility. Specifically, the characteristic curvature ofsurfactants should match the hydrophobicity of oils in a specificsystem.

The present disclosure provides an oral care composition containing anon-ionic surfactant component comprising (i) a surfactant selected fromthe group consisting of:poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymers,poly(oxyethylene)-modified hydrogenated castor oils, andpoly(oxyethylene)-modified fatty acid monoesters of sorbitan, and (ii) asurfactant selected from the group consisting of polyol esters and sugaresters, having a high antimicrobial efficacy, having acceptableoff-taste and organoleptic properties. Without intending to be limitedto any particular theory, the combination of the surfactant and thepolyol ester or sugar ester give high solublization capacity for theactive ingredients.

Accordingly, one aspect presented herein, provides an oral carecomposition, comprising:

-   -   a) a bioactive component in an amount from 0.01 to 10 wt % of        the oral care composition;    -   b) a non-ionic surfactant comprising (i) a surfactant selected        from the group consisting of:        poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block        copolymers, poly(oxyethylene)-modified hydrogenated castor oils,        and poly(oxyethylene)-modified fatty acid monoesters of        sorbitan, and (ii) a surfactant selected from the group        consisting of polyol esters and sugar esters;    -   c) at least one orally acceptable solvent; and optionally,    -   d) a C₂-C₄ monohydric alcohol,        -   wherein the ratio of the surfactant selected from the group            consisting of:            poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block            copolymers, poly(oxyethylene)-modified hydrogenated castor            oils, and poly(oxyethylene)-modified fatty acid monoesters            of sorbitan to the surfactant selected from the group            consisting of polyol esters and sugar esters is from 1:10 to            10:1; and        -   wherein the ratio of the non-ionic surfactant to the            bioactive component is from 0.5 to 3.

As used herein, the term “oral care composition” refers to a product,which in the ordinary course of usage, is not intentionally swallowedfor purposes of systemic administration of particular therapeuticagents, but is rather retained in the oral cavity for a time sufficientto contact substantially all of the dental surfaces and/or oral tissuesfor purposes of oral activity. The oral care composition may be invarious forms including toothpaste, dentifrice, tooth gel, subgingivalgel, mouth rinse, solutions, mousse, foam, denture care product, mouthspray, lozenge or chewable tablet. The oral care composition may also beincorporated onto floss, strips or films for direct application orattachment to oral surfaces or integrated into a device or applicatorsuch as a toothbrush or roll-ons. Such applicators may be for single ormultiple use.

As used herein, the term “dentifrice” includes paste, gel, or liquidformulations unless otherwise specified. The dentifrice composition maybe a single phase composition or may be a combination of two or moreseparate dentifrice compositions. The dentifrice composition may be inany desired form, such as deep striped, surface striped, multilayered,having a gel surrounding a paste, or any combination thereof. Eachdentifrice composition in a dentifrice comprising two or more separatedentifrice compositions may be contained in a physically separatedcompartment of a dispenser and dispensed side-by-side.

As used herein, the term “dispenser” refers to any pump, tube, orcontainer suitable for dispensing compositions such as dentifrices.

The phrase “reduced level” of alcohol means an amount of a C₂-C₄monohydric alcohol up to 10% v/v (or about 10% v/v), optionally, up to5% v/v (or about 5% v/v), optionally, up to 1.0% v/v (or about 1.0%v/v), optionally up to 0.1% v/v (or about 0.1% v/v) by volume of thetotal oral care composition. In some aspects, the oral care compositionsof the present disclosure are free of C₂-C₄ monohydric alcohols.

It has been shown that microemulsions according to the presentdisclosure are transparent at room temperature (RT). The termtransparent means that the microemulsions in the absence of coloring orfluorescent agents have nephelometric turbidity units (NTU) below 20NTU, alternatively below 10 NTU, alternatively below 8 NTU.

The Bioactive Component

In some aspects, the oral care composition comprises a bioactivecomponent. In some aspects, the amount of the bioactive component in theoral care composition is from 0.01 to 10 wt % of the oral carecomposition. Alternatively, in some aspects, the amount of the bioactivecomponent in the oral care composition is from 0.01 to 9 wt % of theoral care composition. Alternatively, in some aspects, the amount of thebioactive component in the oral care composition is from 0.01 to 8 wt %of the oral care composition. Alternatively, in some aspects, the amountof the bioactive component in the oral care composition is from 0.01 to7 wt % of the oral care composition. Alternatively, in some aspects, theamount of the bioactive component in the oral care composition is from0.01 to 6 wt % of the oral care composition. Alternatively, in someaspects, the amount of the bioactive component in the oral carecomposition is from 0.01 to 5 wt % of the oral care composition.Alternatively, in some aspects, the amount of the bioactive component inthe oral care composition is from 0.01 to 4 wt % of the oral carecomposition. Alternatively, in some aspects, the amount of the bioactivecomponent in the oral care composition is from 0.01 to 3 wt % of theoral care composition. Alternatively, in some aspects, the amount of thebioactive component in the oral care composition is from 0.01 to 2 wt %of the oral care composition. Alternatively, in some aspects, the amountof the bioactive component in the oral care composition is from 0.01 to1 wt % of the oral care composition. Alternatively, in some aspects, theamount of the bioactive component in the oral care composition is from0.01 to 0.9 wt % of the oral care composition. Alternatively, in someaspects, the amount of the bioactive component in the oral carecomposition is from 0.01 to 0.8 wt % of the oral care composition.Alternatively, in some aspects, the amount of the bioactive component inthe oral care composition is from 0.01 to 0.7 wt % of the oral carecomposition. Alternatively, in some aspects, the amount of the bioactivecomponent in the oral care composition is from 0.01 to 0.6 wt % of theoral care composition. Alternatively, in some aspects, the amount of thebioactive component in the oral care composition is from 0.01 to 0.5 wt% of the oral care composition. Alternatively, in some aspects, theamount of the bioactive component in the oral care composition is from0.01 to 0.4 wt % of the oral care composition. Alternatively, in someaspects, the amount of the bioactive component in the oral carecomposition is from 0.01 to 0.3 wt % of the oral care composition.Alternatively, in some aspects, the amount of the bioactive component inthe oral care composition is from 0.01 to 0.2 wt % of the oral carecomposition. Alternatively, in some aspects, the amount of the bioactivecomponent in the oral care composition is from 0.01 to 0.1 wt % of theoral care composition. Alternatively, in some aspects, the amount of thebioactive component in the oral care composition is from 0.01 to 0.09 wt% of the oral care composition. Alternatively, in some aspects, theamount of the bioactive component in the oral care composition is from0.01 to 0.08 wt % of the oral care composition. Alternatively, in someaspects, the amount of the bioactive component in the oral carecomposition is from 0.01 to 0.07 wt % of the oral care composition.Alternatively, in some aspects, the amount of the bioactive component inthe oral care composition is from 0.01 to 0.06 wt % of the oral carecomposition. Alternatively, in some aspects, the amount of the bioactivecomponent in the oral care composition is from 0.01 to 0.05 wt % of theoral care composition. Alternatively, in some aspects, the amount of thebioactive component in the oral care composition is from 0.01 to 0.04 wt% of the oral care composition. Alternatively, in some aspects, theamount of the bioactive component in the oral care composition is from0.01 to 0.03 wt % of the oral care composition. Alternatively, in someaspects, the amount of the bioactive component in the oral carecomposition is from 0.01 to 0.02 wt % of the oral care composition.

In some aspects, the amount of the bioactive component in the oral carecomposition is from 0.02 to 10 wt % of the oral care composition.Alternatively, in some aspects, the amount of the bioactive component inthe oral care composition is from 0.03 to 10 wt % of the oral carecomposition. Alternatively, in some aspects, the amount of the bioactivecomponent in the oral care composition is from 0.04 to 10 wt % of theoral care composition. Alternatively, in some aspects, the amount of thebioactive component in the oral care composition is from 0.05 to 10 wt %of the oral care composition. Alternatively, in some aspects, the amountof the bioactive component in the oral care composition is from 0.06 to10 wt % of the oral care composition. Alternatively, in some aspects,the amount of the bioactive component in the oral care composition isfrom 0.07 to 10 wt % of the oral care composition. Alternatively, insome aspects, the amount of the bioactive component in the oral carecomposition is from 0.08 to 10 wt % of the oral care composition.Alternatively, in some aspects, the amount of the bioactive component inthe oral care composition is from 0.09 to 10 wt % of the oral carecomposition. Alternatively, in some aspects, the amount of the bioactivecomponent in the oral care composition is from 0.1 to 10 wt % of theoral care composition. Alternatively, in some aspects, the amount of thebioactive component in the oral care composition is from 0.2 to 10 wt %of the oral care composition. Alternatively, in some aspects, the amountof the bioactive component in the oral care composition is from 0.3 to10 wt % of the oral care composition. Alternatively, in some aspects,the amount of the bioactive component in the oral care composition isfrom 0.4 to 10 wt % of the oral care composition. Alternatively, in someaspects, the amount of the bioactive component in the oral carecomposition is from 0.5 to 10 wt % of the oral care composition.Alternatively, in some aspects, the amount of the bioactive component inthe oral care composition is from 0.6 to 10 wt % of the oral carecomposition. Alternatively, in some aspects, the amount of the bioactivecomponent in the oral care composition is from 0.7 to 10 wt % of theoral care composition. Alternatively, in some aspects, the amount of thebioactive component in the oral care composition is from 0.8 to 10 wt %of the oral care composition. Alternatively, in some aspects, the amountof the bioactive component in the oral care composition is from 0.9 to10 wt % of the oral care composition. Alternatively, in some aspects,the amount of the bioactive component in the oral care composition isfrom 1 to 10 wt % of the oral care composition. Alternatively, in someaspects, the amount of the bioactive component in the oral carecomposition is from 2 to 10 wt % of the oral care composition.Alternatively, in some aspects, the amount of the bioactive component inthe oral care composition is from 3 to 10 wt % of the oral carecomposition. Alternatively, in some aspects, the amount of the bioactivecomponent in the oral care composition is from 4 to 10 wt % of the oralcare composition. Alternatively, in some aspects, the amount of thebioactive component in the oral care composition is from 5 to 10 wt % ofthe oral care composition. Alternatively, in some aspects, the amount ofthe bioactive component in the oral care composition is from 6 to 10 wt% of the oral care composition. Alternatively, in some aspects, theamount of the bioactive component in the oral care composition is from 7to 10 wt % of the oral care composition. Alternatively, in some aspects,the amount of the bioactive component in the oral care composition isfrom 8 to 10 wt % of the oral care composition. Alternatively, in someaspects, the amount of the bioactive component in the oral carecomposition is from 9 to 10 wt % of the oral care composition.

In some aspects, the amount of the bioactive component in the oral carecomposition is 0.01, or 0.02, or 0.03, or 0.04, or 0.05, or 0.06, or0.07, or 0.08, or 0.09, or 0.1, or 0.2, or 0.3, or 0.4, or 0.5, or 0.6,or 0.7, or 0.8, or 0.9, or 1, or 2, or 3, or 4, or 5, or 6, or 7, or 8,or 9, or 10 wt % of the oral care composition.

As used herein, the term “bioactive component” refers to at least onewater-insoluble agent that imparts at least one activity selected fromthe group consisting of: an anticaries activity, an antiplaque activity,an antigingivitis activity or a gum disease treatment, an antimicrobialactivity, and a flavor.

In some embodiments, the bioactive component is an essential oil.Non-limiting examples of essential oils include: Thymol,[(CH₃)₂CHC₆H₃(CH₃)OH, also known as isopropyl-m-cresol], Methylsalicylate, [C₆H₄OHCOOCH₃, also known as wintergreen oil], Eucalyptol(C₁₀H₁₈O, also known as cineol), and Menthol (CH₃C₆H₉(C₃H₇)OH), alsoknown as hexahydrothymol).

In some embodiments, the bioactive component is at least one agentselected from the group consisting of: menthol, methyl salicylate,thymol and eucalyptol. In some aspects, the bioactive componentcomprises menthol, methyl salicylate, thymol and eucalyptol.

In some aspects, the bioactive component comprises at least onebioactive agent disclosed in U.S. Patent Application Publication No.2016/01425203.

In some aspects, the bioactive component comprises at least onebioactive agent disclosed in U.S. Patent Application Publication No.2015/0306007.

In some aspects, the bioactive component comprises at least onebioactive agent disclosed in U.S. Patent Application Publication No.2007/0190080.

In some aspects, the bioactive component comprises at least onebioactive agent disclosed in U.S. Patent Application Publication No.2014/0242003.

In some aspects, the bioactive component comprises at least onebioactive agent disclosed in U.S. Patent Application Publication No.2014/0286880.

In some aspects, the bioactive component comprises at least onebioactive agent disclosed in U.S. Patent Application Publication No.2013/0280180.

In some aspects, the bioactive component comprises at least onebioactive agent disclosed in U.S. Pat. No. 6,348,187.

In some aspects, the bioactive component comprises at least onebioactive agent disclosed in U.S. Pat. No. 5,817,295.

In some aspects, the bioactive component comprises at least onebioactive agent disclosed in U.S. Pat. No. 5,292,527.

The Non-Ionic Surfactant Component

In some aspects, the oral care composition comprises a non-ionicsurfactant component, comprising (i) a surfactant selected from thegroup consisting of:poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymers,poly(oxyethylene)-modified hydrogenated castor oils, andpoly(oxyethylene)-modified fatty acid monoesters of sorbitan, and (ii) asurfactant selected from the group consisting of polyol esters and sugaresters.

In some aspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 0.5 to 3. Alternatively, in some aspects, the ratio ofthe non-ionic surfactant to the bioactive component is from 0.6 to 3.Alternatively, in some aspects, the ratio of the non-ionic surfactant tothe bioactive component is from 0.6 to 3. Alternatively, in someaspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 0.8 to 3. Alternatively, in some aspects, the ratio ofthe non-ionic surfactant to the bioactive component is from 0.9 to 3.Alternatively, in some aspects, the ratio of the non-ionic surfactant tothe bioactive component is from 1 to 3. Alternatively, in some aspects,the ratio of the non-ionic surfactant to the bioactive component is from1.1 to 3. Alternatively, in some aspects, the ratio of the non-ionicsurfactant to the bioactive component is from 1.2 to 3. Alternatively,in some aspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 1.3 to 3. Alternatively, in some aspects, the ratio ofthe non-ionic surfactant to the bioactive component is from 1.4 to 3.Alternatively, in some aspects, the ratio of the non-ionic surfactant tothe bioactive component is from 1.5 to 3. Alternatively, in someaspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 1.6 to 3. Alternatively, in some aspects, the ratio ofthe non-ionic surfactant to the bioactive component is from 1.7 to 3.Alternatively, in some aspects, the ratio of the non-ionic surfactant tothe bioactive component is from 1.8 to 3. Alternatively, in someaspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 1.9 to 3. Alternatively, in some aspects, the ratio ofthe non-ionic surfactant to the bioactive component is from 2 to 3.Alternatively, in some aspects, the ratio of the non-ionic surfactant tothe bioactive component is from 2.1 to 3. Alternatively, in someaspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 2.2 to 3. Alternatively, in some aspects, the ratio ofthe non-ionic surfactant to the bioactive component is from 2.3 to 3.Alternatively, in some aspects, the ratio of the non-ionic surfactant tothe bioactive component is from 2.4 to 3. Alternatively, in someaspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 2.5 to 3. Alternatively, in some aspects, the ratio ofthe non-ionic surfactant to the bioactive component is from 2.6 to 3.Alternatively, in some aspects, the ratio of the non-ionic surfactant tothe bioactive component is from 2.7 to 3. Alternatively, in someaspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 2.8 to 3. Alternatively, in some aspects, the ratio ofthe non-ionic surfactant to the bioactive component is from 2.9 to 3.

In some aspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 0.5 to 2.9. Alternatively, in some aspects, the ratioof the non-ionic surfactant to the bioactive component is from 0.5 to2.8. Alternatively, in some aspects, the ratio of the non-ionicsurfactant to the bioactive component is from 0.5 to 2.7. Alternatively,in some aspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 0.5 to 2.6. Alternatively, in some aspects, the ratioof the non-ionic surfactant to the bioactive component is from 0.5 to2.5. Alternatively, in some aspects, the ratio of the non-ionicsurfactant to the bioactive component is from 0.5 to 2.4. Alternatively,in some aspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 0.5 to 2.3. Alternatively, in some aspects, the ratioof the non-ionic surfactant to the bioactive component is from 0.5 to2.2. Alternatively, in some aspects, the ratio of the non-ionicsurfactant to the bioactive component is from 0.5 to 2.1. Alternatively,in some aspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 0.5 to 2. Alternatively, in some aspects, the ratio ofthe non-ionic surfactant to the bioactive component is from 0.5 to 1.9.Alternatively, in some aspects, the ratio of the non-ionic surfactant tothe bioactive component is from 0.5 to 1.8. Alternatively, in someaspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 0.5 to 1.7. Alternatively, in some aspects, the ratioof the non-ionic surfactant to the bioactive component is from 0.5 to1.6. Alternatively, in some aspects, the ratio of the non-ionicsurfactant to the bioactive component is from 0.5 to 1.5. Alternatively,in some aspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 0.5 to 1.4. Alternatively, in some aspects, the ratioof the non-ionic surfactant to the bioactive component is from 0.5 to1.3. Alternatively, in some aspects, the ratio of the non-ionicsurfactant to the bioactive component is from 0.5 to 1.2. Alternatively,in some aspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 0.5 to 1.1. Alternatively, in some aspects, the ratioof the non-ionic surfactant to the bioactive component is from 0.5 to 1.Alternatively, in some aspects, the ratio of the non-ionic surfactant tothe bioactive component is from 0.5 to 0.9. Alternatively, in someaspects, the ratio of the non-ionic surfactant to the bioactivecomponent is from 0.5 to 0.8. Alternatively, in some aspects, the ratioof the non-ionic surfactant to the bioactive component is from 0.5 to0.7. Alternatively, in some aspects, the ratio of the non-ionicsurfactant to the bioactive component is from 0.5 to 0.6.

In some aspects, the ratio of the non-ionic surfactant to the bioactivecomponent is 0.5, 0.6, or 0.7, or 0.8, or 0.9, or 1, or 1.1, or 1.2, or1.3, or 1.4, or 1.5, or 1.6, or 1.7, or 1.8, or 1.9, or 2, or 2.1, or2.2, or 2.3, or 2.4, or 2.5, or 2.6, or 2.7, or 2.8, or 2.9, or 3.

In some aspects, thepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymeris the hydrophilic non-ionic surfactant sold under the tradenamePoloxamer 407, comprising a triblock copolymer consisting of a centralhydrophobic block of polypropylene glycol flanked by two hydrophilicblocks of polyethylene glycol (PEG).

In some aspects, thepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymeris the hydrophilic non-ionic surfactant sold under the tradenameKolliphor 40, comprising poly(oxyethylene) hydrogenated castor oil.

In some aspects, thepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymercomprises at least onepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymerdisclosed in U.S. Patent Application Publication No. 2016/01425203.

In some aspects, thepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymercomprises at least onepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymerdisclosed in U.S. Patent Application Publication No. 2015/0306007.

In some aspects, thepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymercomprises at least onepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymerdisclosed in U.S. Patent Application Publication No. 2014/0242003.

In some aspects, thepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymercomprises at least onepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymerdisclosed in U.S. Patent Application Publication No. 2014/0286880.

In some aspects, thepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymercomprises at least onepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymerdisclosed in U.S. Pat. No. 5,817,295.

In some aspects, thepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymercomprises at least onepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymerdisclosed in U.S. Pat. No. 5,292,527.

In some aspects, the poly(oxyethylene)-modified fatty acid monoester ofsorbitan is Tween 80.

In some aspects, the poly(oxyethylene)-modified fatty acid monoester ofsorbitan is Tween 20.

In some aspects, the sugar ester is selected from the group consistingof: sucrose laurate, sucrose monolaurate, sucrose palmitate, sucrosemonopalmitate, and combinations thereof.

In some aspects, the sugar ester is a sucrose ester. In an alternateaspect, the sugar ester is a fructose ester.

In some aspects, the polyol ester is a glycerol ester.

In some aspects, the polyol ester is monolauric acid decaglycerin ester.

In some aspects, the ratio of the surfactant selected from the groupconsisting of: poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene)block copolymers, poly(oxyethylene)-modified hydrogenated castor oils,and poly(oxyethylene)-modified fatty acid monoesters of sorbitan to thesurfactant selected from the group consisting of polyol esters and sugaresters is from 1:5 to 5:1.

In some aspects, the ratio of the surfactant selected from the groupconsisting of: poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene)block copolymers, poly(oxyethylene)-modified hydrogenated castor oils,and poly(oxyethylene)-modified fatty acid monoesters of sorbitan to thesurfactant selected from the group consisting of polyol esters and sugaresters is from 1:3 to 3:1.

Flavor Systems

In some aspects, the composition further comprises a flavor system. Theflavor system may mask any unpleasant taste and sensations due tocertain components of the composition such as antimicrobial actives orperoxide. Without intending to be limited to any particular theory,pleasant tasting compositions improve user compliance to prescribed orrecommended use of oral care products. The present flavor system mayalso comprise traditional flavor components, in particular those thatare relatively stable in the presence of usual oral care product carriermaterials or excipients. The combination of the selected flavoringsystem with the compositions presented herein may provide a high-impactrefreshing sensation with a well-rounded flavor profile.

In some aspects, the flavor system may comprise additional flavoringredients including but not limited to peppermint oil, corn mint oil,spearmint oil, oil of wintergreen, clove bud oil, cassia, sage, parsleyoil, marjoram, lemon, lime, orange, cis-jasmone,2,5-dimethyl-4-hydroxy-3(2H)-furanone,5-ethyl-3-hydroxy-4-methyl-2(5H)-furanone, vanillin, ethyl vanillin,anisaldehyde, 3,4-methylenedioxybenzaldehyde, 3,4-dimethoxybenzaldehyde,4-hydroxybenzaldehyde, 2-methoxybenzaldehyde, benzaldehyde;cinnamaldehyde, hexyl cinnamaldehyde, alpha-methyl cinnamaldehyde,ortho-methoxy cinnamaldehyde, alpha-amyl cinnamaldehydepropenylguaethol, heliotropine, 4-cis-heptenal, diacetyl, methyl-p-tert-butylphenyl acetate, menthol, methyl salicylate, ethyl salicylate, 1-menthylacetate, oxanone, alpha-irisone, methyl cinnamate, ethyl cinnamate,butyl cinnamate, ethyl butyrate, ethyl acetate, methyl anthranilate,iso-amyl acetate, iso-amyl butyrate, allyl caproate, eugenol,eucalyptol, thymol, cinnamic alcohol, octanol, octanal, decanol,decanal, phenylethyl alcohol, benzyl alcohol, alpha-terpineol, linalool,limonene, citral, maltol, ethyl maltol, anethole, dihydroanethole,carvone, menthone, β-damascenone, ionone, gamma decalactone, gammanonalactone, gamma undecalactone and mixtures thereof.

Generally suitable flavoring ingredients are those containing structuralfeatures and functional groups that are less prone to redox reactions.These include derivatives of flavor chemicals that are saturated orcontain stable aromatic rings or ester groups. Also suitable are flavorchemicals that may undergo some oxidation or degradation withoutresulting in a significant change in the flavor character or profile.The flavor ingredients may be supplied in the composition as single orpurified chemicals or by addition of natural oils or extracts that havepreferably undergone a refining treatment to remove components that arerelatively unstable and may degrade and alter the desired flavorprofile, resulting in a less acceptable product from an organolepticstandpoint. Flavoring agents may generally be used in the compositionsat levels of from about 0.001% to about 5%, by weight of thecomposition.

In some aspects, the flavor system may further include a sweeteningagent. Suitable sweeteners include those well known in the art,including both natural and artificial sweeteners. Some suitablewater-soluble sweeteners include monosaccharides, disaccharides andpolysaccharides such as xylose, ribose, glucose (dextrose), mannose,galactose, fructose (levulose), sucrose (sugar), maltose, invert sugar(a mixture of fructose and glucose derived from sucrose), partiallyhydrolyzed starch, corn syrup solids, dihydrochalcones, monellin,steviosides, and glycyrrhizin. Suitable water-soluble artificialsweeteners include soluble saccharin salts, i.e., sodium or calciumsaccharin salts, cyclamate salts, the sodium, ammonium or calcium saltof 3,4-dihydro-6-methyl-1,2,3-oxathiazine-4-one-2,2-dioxide, thepotassium salt of3,4-dihydro-6-methyl-1,2,3-oxathiazine-4-one-2,2-dioxide (acesulfame-K),the free acid form of saccharin, and the like. Other suitable sweetenersinclude dipeptide based sweeteners, such as L-aspartic acid derivedsweeteners, such as L-aspartyl-L-phenylalanine methyl ester (aspartame)and materials described in U.S. Pat. No. 3,492,131,L-alpha-aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alaninamidehydrate, methyl esters of L-aspartyl-L-phenylglycerin andL-aspartyl-L-2,5,dihydrophenyl-glycine,L-aspartyl-2,5-dihydro-L-phenylalanine,L-aspartyl-L-(1-cyclohexylen)-alanine, and the like. Water-solublesweeteners derived from naturally occurring water-soluble sweeteners,such as a chlorinated derivative of ordinary sugar (sucrose), known, forexample, under the product description of sucralose as well as proteinbased sweeteners such as thaumatoccous danielli (Thaumatin I and II) canbe used.

In some aspects, the composition may contains from about 0.1% to about10% of sweetener, alternatively from about 0.1% to about 1%, by weightof the composition.

In some aspects, the flavor system may further include salivatingagents, warming agents, and numbing agents. These agents may be presentin the compositions at a level of from about 0.001% to about 10%,alternatively from about 0.1% to about 1%, by weight of the composition.

Suitable salivating agents include Jambu® manufactured by Takasago.Suitable numbing agents include benzocaine, lidocaine, clove bud oil,and ethanol. Examples of warming agents include ethanol, capsicum andnicotinate esters, such as benzyl nicotinate.

In addition to the components described above, the present compositionsmay comprise additional optional components and/or orally acceptablecarrier materials.

Orally Acceptable Solvents

In some aspects, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 90 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 85 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 80 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 75 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 70 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 65 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 60 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 55 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 50 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 45 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 40 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 35 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 25 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 20 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 15 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 10 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 9 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 8 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 7 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 6 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 5 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 4 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 3 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 1 to 2 wt % of the oral care composition.

In some aspects, the amount of the orally acceptable solvent in the oralcare composition is from 2 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 3 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 4 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 5 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 6 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 7 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 8 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 9 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 10 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 15 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 20 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 25 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 30 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 35 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 40 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 45 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 50 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 55 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 60 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 65 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 70 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 75 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 80 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 85 to 95 wt % of the oral care composition.Alternatively, the amount of the orally acceptable solvent in the oralcare composition is from 90 to 95 wt % of the oral care composition.

In some aspects, the amount of the orally acceptable solvent in the oralcare composition is 1, or 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9,or 10, or 15, or 20, or 25, or 30, or 40, or 45, or 50, or 55, or 60, or65, or 70, or 75, or 80, or 85, or 90, or 95 wt % of the oral carecomposition.

In some aspects, the orally acceptable solvent is selected from thegroup consisting of: water, polyol, sugar alcohols, a C₁₋₆ linear orbranched alkyl lactate, triacetine, triethylcitrate, benzylic alcohol,and combinations thereof.

In some aspects, the polyol is selected from the group consisting of:polyhydric alcohols, polyalkylene glycols, polyhydric alcohol esters,polyhydric alcohol ethers, and combinations thereof.

In some aspects, the polyhydric alcohol is selected from the groupconsisting of: glycerol, butylene glycol, hexylene glycol,1,3-propanediol, propylene glycol, and combinations thereof.

In some aspects, the polyhydric alcohol is propylene glycol.

In some aspects, the polyhydric alcohol ester and polyhydric alcoholether are selected from the group consisting of: dipropylene glycol,ethoxydiglycol, and combinations thereof.

In some aspects, the polyalkylene glycol is selected from the groupconsisting of: polyethylene glycol, polypropylene glycol, andcombinations thereof.

In some aspects, the sugar alcohol is selected from the group consistingof: xylitol, sorbitol, mannitol, maltitol, inositol, allitol, altritol,dulcitol, galactitol, glucitol, hexitol, iditol, pentitol, ribitol,erythritol and mixtures thereof.

In some aspects, the sugar alcohol is selected from the group consistingof sorbitol and xylitol or mixtures thereof.

In some aspects, the C₁₋₆ linear or branched alkyl lactate is ethyllactate.

Additional Optional Components

The oral care compositions of the present disclosure may also includeone or more optional ingredients nonexclusively including a thickeningagent, colorants, additional humectants, chelating agents, coolingagents, whitening agents, and additives such as preservatives, pHadjusting agents, and the like.

In some aspects, the pH of the oral care compositions of the presentdisclosure is maintained at range of below 5 (or about 5),alternatively, below 4.5 (or about 4.5) or, alternatively, in the rangeof from 4.4 (or about 4.4) to 3 (or about 3), or alternatively in therange of from 3.5 (or about 3.5) to 4.4 (or about 4.4).

In some aspects, the pH of the oral care composition may be adjusted bythe addition of an amount of benzoic acid to adjust the pH of the oralcare composition to the desired pH.

In some aspects, the effective amount of the sodium benzoate is from 0to 0.2 wt % of the oral care composition. In some aspects, the effectiveamount of the sodium benzoate is from 0.05 to 0.1 wt % of the oral carecomposition.

Commercially available thickening agents, which are capable of impartingthe appropriate viscosity to the compositions, are suitable for use inthe oral care compositions presented herein. Examples of suitablethickening agents nonexclusively include: mono or diesters of 1)polyethylene glycol of formula: HO—(CH₂CH₂O)_(z)H, wherein z is aninteger from about 3 to about 200; and 2) fatty acids containing fromabout 16 to about 22 carbon atoms; fatty acid esters of ethoxylatedpolyols; ethoxylated derivatives of mono and diesters of fatty acids andglycerine; hydroxyalkyl cellulose; alkyl cellulose; hydroxyalkyl alkylcellulose; and mixtures thereof. Preferred thickeners includepolyethylene glycol ester, and more preferably PEG-150 distearate whichis available from the Stepan Company of Northfield, Ill. or from Comiel,S.p.A. of Bologna, Italy under the trade name, “PEG 6000 DS”.

Examples of suitable chelating agents include those which are capable ofprotecting and preserving the oral care compositions according to theaspects presented herein. In some aspects, the chelating agent isethylenediamine tetracetic acid (“EDTA”), alternatively tetrasodiumEDTA, available commercially from Dow Chemical Company of Midland, Mich.under the trade name, “Versene 100XL” and is present in an amount, basedupon the total weight of the composition, from about 0 to about 0.5 wt%, alternatively from about 0.05 wt % to about 0.25 wt %.

Suitable preservatives include, but are not limited to, sodium benzoate,and polysorbate and are present in the composition in an amount, basedupon the total weight of the composition, from about 0 to about 0.2 wt%, alternatively from about 0.05 wt % to about 0.10 wt %.

In some aspects, the oral care composition comprises at least onecooling compound. Cooling compounds or compounds that have aphysiological cooling effect on oral surfaces are common ingredients ina wide variety of products including edible compositions and personalcare products and in flavor or perfume compositions for use in suchproducts. Examples of edible compositions include confectionery,candies, chocolate, chewing gum, beverages and oral medicines. A classof topically applied compositions to which the present disclosurerelates is for oral and throat care, which include products in powder,paste or liquid forms and which on being used are retained for a timesufficient to contact the surface and the internal mucous membrane ofthe oral cavities or the pharynx. Such products include for example,mouthwashes, dental and throat lozenges, gargles, chewing gum,dentifrice or toothpastes, toothpicks, dental tablets and powders andtopical solutions for application in dental treatment, as well ascough-syrups, chewable antacids and digestion promoting preparations.

The pleasant cooling sensation provided by cooling compounds contributesto the appeal and acceptability of the products. In particular, oralcare products such as dentifrices and mouthwashes are formulated withcoolants because they provide breath freshening effects and a clean,cool, fresh feeling in the mouth.

Without intending to be limited to any particular theory, sensationssuch as cool or cold can be attributed to activation of receptors atperipheral nerve fibers by a stimulus such as low temperature or achemical coolant, which produces electrochemical signals that travel tothe brain, which then interprets, organizes and integrates the incomingsignal(s) into a perception or sensation. Different classes of receptorshave been implicated in sensing cold temperatures or chemical coolantstimuli at mammalian sensory nerve fibers. Among these receptors, onecandidate involved in sensing cold has been identified and designated ascold- and menthol-sensitive receptor (CMR1) or TRPM8.

The TRPM8 nomenclature for the receptor comes from its characterizationas a non-selective cation channel of the transient receptor potential(TRP) family that is activated by stimuli including low temperatures,menthol and other chemical coolants. However, the precise mechanismsunderlying the perception of a pleasant cooling sensation on skin ororal surfaces are presently not clearly understood.

Without intending to be limited to any particular theory, while it hasbeen demonstrated that the TRPM8 receptor is activated by menthol andother coolants, it is not fully understood what other receptors may beinvolved and to what extent these receptors need to be stimulated orperhaps suppressed in order that the overall perceived sensation wouldbe pleasant, cooling and refreshing. For example, menthol is widely usedas a cooling agent, but menthol can also produce other sensationsincluding tingling, burning, prickling and stinging as well as a mintysmell and bitter taste. Thus, it can be inferred that menthol, and othercooling agents may act on many different receptors, including cold,warm, pain and taste receptors.

However, it is not readily discernible how to isolate which receptoractivities would result in a specific sensation such as pleasant coolingwithout the undesirable sensations such as bitterness or irritation.Neither is it apparent how to control the activity of coolants or othersensory agents such that only the desired sensation is elicited from useof a particular sensory agent. The present disclosure is thus based onthe discovery of agents that can be used to enhance and/or modulate theactivity of cooling and flavoring compounds.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin International Patent Application Publication No. WO2014090293.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin International Patent Application Publication No. WO2012061698.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Patent Application Publication No. 2010007608.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Patent Application Publication No. 20080319055.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Patent Application Publication No. 20080311232.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Patent Application Publication No. 20090054520.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Patent Application Publication No. 20080177800.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Patent Application Publication No. 20080096969.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin International Patent Application Publication No. WO2010128026.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin International Patent Application Publication No. WO2011061330.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin International Patent Application Publication No. WO2011138696.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Pat. No. 8,377,422.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin International Patent Application Publication No. WO2013033501.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Patent Application Publication No. 20130216486.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Pat. No. 7,935,848.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Patent Application Publication No. 20130345300.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin International Patent Application Publication No. WO2013080830.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin International Patent Application Publication No. WO2014010657.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Patent Application Publication No. 20140219930.

Examples of cooling compounds suitable for inclusion into the oral carecompositions according to certain aspects presented herein are disclosedin U.S. Patent Application Publication No. 20150139918.

In some aspects, the at least one cooling compound is selected from thegroup consisting of:2-(4-ethylphenoxy)-N-(1H-pyrazol-5-yl)-N-(2-thienylmethyl)acetamide,WS-23 (2-Isopropyl-N,2,3-trimethylbutyramide), FEMA 3804; WS-3(N-Ethyl-p-menthane-3-carboxamide), FEMA 3455; WS-5 [Ethyl3-(p-menthane-3-carboxamido)acetate], FEMA 4309; WS-12(1R,2S,5R)-N-(4-Methoxyphenyl)-p-menthanecarboxamide, FEMA 4681;WS-(N-Ethyl-2,2-diisopropylbutanamide), FEMA 4557;N-Cyclopropyl-5-methyl-2-isopropylcyclohexanecarboxamide, FEMA 4693,WS-116 (N-(1,1-Dimethyl-2-hydroxyethyl)-2,2-diethylbutanamide),N-(1,1-Dimethyl-2-hydroxyethyl)2,2-diethylbutanamide, FEMA 4603,Menthoxyethanol, FEMA 4154,N-(4-cyanomethylphenyl)-p-menthanecarboxamide, FEMA 4496;N-(2-(Pyridin-2-yl)ethyl)-3-p-menthanecarboxamide, FEMA 4549;N-(2-Hydroxyethyl)-2-isopropyl-2,3-dimethylbutanamide, FEMA 4602 and(also N-(4-(carbamoylmethyl)phenyl)-menthylcarboxamide, FEMA 4684;(1R,2S,5R)-N-(4-Methoxyphenyl)-p-menthanecarboxamide (WS-12), FEMA 4681;(2S,5R)-N-[4-(2-Amino-2-oxoethyl)phenyl]-p-menthanecarboxamide, FEMA4684; andN-Cyclopropyl-5-methyl-2-isopropylcyclohexanecarbonecarboxamide, FEMA4693; 2-[(2-p-Menthoxy)ethoxy]ethanol, FEMA 4718;(2,6-Diethyl-5-isopropyl-2-methyltetrahydropyran, FEMA 4680);trans-4-tert-Butylcyclohexanol, FEMA 4724;2-(p-tolyloxy)-N-(1H-pyrazol-5-yl)-N-((thiophen-2-yl)methyl)acetamide,FEMA 4809; Menthone glycerol ketal, FEMA 3807; Menthone glycerol ketal,FEMA 3748; (−)-Menthoxypropane-1,2-diol;3-(1-Menthoxy)-2-methylpropane-1,2-diol, FEMA 3849; Isopulegol; (+)-cis& (−)-trans p-Menthane-3,8-diol, Ratio ˜62:38, FEMA 4053;2,3-dihydroxy-p-menthane; 3,3,5-trimethylcyclohexanone glycerol ketal;menthyl pyrrolidone carboxylate;(1R,3R,4S)-3-menthyl-3,6-dioxaheptanoate; (1R,2S,5R)-3-menthylmethoxyacetate; (1R,2S,5R)-3-menthyl 3,6,9-trioxadecanoate;(1R,2S,5R)-3-menthyl 3.6,9-trioxadecanoate; (1R,2S,5R)-3-menthyl(2-hydroxyethoxy)acetate; (1R,2S,5R)-menthyl11-hydroxy-3,6,9-trioxaundecanoate; Cubebol, FEMA 4497;N-(4-cyanomethylphenyl) p-menthanecarboxamide, FEMA 4496;2-isopropyl-5-methylcyclohexyl 4-(dimethylamino)-4-oxobutanoate, FEMA4230; N-(4-cyanomethylphenyl) p-menthanecarboxamide, FEMA 4496;N-(2-pyridin-2-ylethyl) p-; menthanecarboxamide, FEMA 4549, Menthyllactate, FEMA 3748; 6-isopropyl-3,9-dimethyl-1,4-dioxaspiro[4.5]decan-2-one, FEMA 4285; N-benzo[1,3]dioxol-5-yl-3-p-menthanecarboxamide;N-(1-isopropyl-1,2-dimethylpropyl)-1,3-benzodioxole-5-carboxamide;N-(R)-2-oxotetrahydrofuran-3-yl-(1R,2S,5R)-p-menthane-3-carboxamide;mixture of 2,2,5,6,6-pentamethyl-2,3,6,6a-tetrahydropentalen-3a(1H)-oland 5-(2-hydroxy-2-methylpropyl)-3,4,4-trimethylcyclopent-2-en-1-one;(1R,2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-2-yl)ethyl)cyclohexanecarboxamide,FEMA 4549;(2S,5R)-2-isopropyl-5-methyl-N-(2-(pyridin-4-yl)ethyl)cyclohexanecarboxamide;N-(4-cyanomethylphenyl) p-menthanecarboxamide, FEMA 4496;(1S,2S,5R)-N-(4-(cyanomethyl)phenyl)-2-isopropyl-5-methylcyclohexanecarboxamide;1/7-isopropyl-4/5-methyl-bicyclo [2.2.2]oct-5-ene derivatives;4-methoxy-N-phenyl-N-[2-(pyridin-2-yl)ethyl]benzamide;4-methoxy-N-phenyl-N-[2-(pyridin-2-yl)ethyl]benzenesulfonamide;4-chloro-N-phenyl-N-[2-(pyridin-2-yl)ethyl]benzenesulfonamide;4-cyano-N-phenyl-N-[2-(pyridin-2-yl)ethyl]benzenesulfonamid;4-((benzhydrylamino)methyl)-2-methoxyphenol;4-((bis(4-methoxyphenyl)-methylamino)-methyl)-2-methoxyphenol;4-((1,2-diphenylethylamino)methyl)-2-methoxyphenol;4-((benzhydryloxy)methyl)-2-methoxyphenol,4-((9H-fluoren-9-ylamino)methyl)-2-methoxyphenol;4-((benzhydrylamino)methyl)-2-ethoxyphenol;1-(4-methoxyphenyl)-2-(1-methyl-1H-benzo[d]imidazol-2-yl)vinyl4-methoxybenzoate;2-(1-isopropyl-6-methyl-1H-benzo[d]imidazol-2-yl)-1-(4-methoxyphenyl)vinyl-4-methoxybenzoate;(Z)-2-(1-isopropyl-5-methyl-1H-benzo[d]imidazol-2-yl)-1-(4-methoxy-phenyl)vinyl-4-methoxybenzoate;3-alkyl-p-methan-3-ol derivatives; derivatives of fenchyl, D-bornyl,L-bornyl, exo-norbornyl, 2-methylisobornyl, 2-ethylfenchyl,2-methylbornyl, cis-pinan-2-yl, verbanyl and isobornyl; menthyl oxamatederivatives; menthyl 3-oxocarboxylic acid esters; Nalpha-(Menthanecarbonyl)amino acid amides; p-menthane carboxamide andWS-23 analogs; (−)-(1R,2R,4S)-dihydroumbellulol; p-menthane alkyloxyamides; cyclohexane derivatives; butone derivatives; a mixture of3-menthoxy-1-propanol and 1-menthoxy-2-propanol;1-[2-hydroxyphenyl]-4-[2-nitrophenyl-]-1,2,3,6-tetrahydropyrimidine-2-one;4-methyl-3-(1-pyrrolidinyl)-2[5H]-furanone; and combinations thereof.

Orally Acceptable Carrier Materials and Products

In some aspects, the orally acceptable carrier may comprise one or morecompatible solid or liquid excipients or diluents which are suitable fortopical oral administration. By “compatible,” as used herein, is meantthat the components of the composition are capable of being commingledwithout interaction in a manner which would substantially reducestability and/or efficacy.

The carriers or excipients of the present disclosure can include theusual and conventional components of dentifrices, non-abrasive gels,subgingival gels, mouthwashes or rinses, mouth sprays, chewing gums,lozenges and breath mints.

The choice of a carrier to be used is basically determined by the waythe composition is to be introduced into the oral cavity. Carriermaterials for toothpaste, tooth gel or the like include abrasivematerials, sudsing agents, binders, humectants, flavoring and sweeteningagents, etc. as disclosed in e.g., U.S. Pat. No. 3,988,433, to Benedict.Carrier materials for biphasic dentifrice formulations are disclosed inU.S. Pat. Nos. 5,213,790; 5,145,666 and 5,281,410 all to Lukacovic etal., and in U.S. Pat. Nos. 4,849,213 and 4,528,180 to Schaeffer.Mouthwash, rinse or mouth spray carrier materials typically includewater, flavoring and sweetening agents, etc., as disclosed in, e.g.,U.S. Pat. No. 3,988,433 to Benedict. Lozenge carrier materials typicallyinclude a candy base; chewing gum carrier materials include a gum base,flavoring and sweetening agents, as in, e.g., U.S. Pat. No. 4,083,955,to Grabenstetter et al. Sachet carrier materials typically include asachet bag, flavoring and sweetening agents. For subgingival gels usedfor delivery of actives into the periodontal pockets or around theperiodontal pockets, a “subgingival gel carrier” is chosen as disclosedin, e.g. U.S. Pat. Nos. 5,198,220 and 5,242,910 both to Damani Carrierssuitable for the preparation of compositions of the present disclosureare well known in the art. Their selection will depend on secondaryconsiderations like taste, cost, and shelf stability, and the like.

Without intending to be limited to any particular theory, thecompositions described in Table 1 may be prepared by mixing thenon-ionic surfactant, aqueous phase (including orally acceptablesolvents and water-soluble components), and water-insoluble compounds,using any conventional mixing technology.

For example, one method may comprise (i) preparing a flavor concentratecomprising surfactants, oil (including menthol, methyl salicylate,thymol, eucalyptol, or other flavor compounds) and a solvent; and (ii)diluting the flavor concentrate into an aqueous phase.

In another example, referring to Example 3, the method may comprise (i)preparing a flavor concentrate comprising a a non-ionic surfactantcomprising (i) a surfactant selected from the group consisting of polyolesters and sugar esters; a flavor component, such as, for example, oil(including menthol, methyl salicylate, thymol, eucalyptol, or otherflavor compounds); and a solvent, and (ii) diluting the flavorconcentrate into an aqueous phase comprising a surfactant selected fromthe group consisting of:poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymers,poly(oxyethylene)-modified hydrogenated castor oils, andpoly(oxyethylene)-modified fatty acid monoesters of sorbitan.

Examples of flavor concentrates suitable for use according toembodiments described herein are disclosed in Table 3.

Methods

In some aspects, methods of use comprise contacting a subject's dentalenamel surfaces and mucosa with the oral compositions described herein.The method of treatment may be by brushing with a dentifrice or rinsingwith a dentifrice slurry or mouthwash. Other methods include contactingthe topical oral gel, denture product, mouthspray, or other form withthe subject's teeth and oral mucosa. The subject may be any person oranimal whose oral cavity is contacted with the oral compositions. Byanimal is meant to include household pets or other domestic animals, oranimals kept in captivity.

One aspect presented herein provides a method for treating plaque,gingivitis or gum disease in a subject in need thereof, comprising thestep of applying to the tissues of the oral cavity of the subject, anamount of the composition according to the aspects presented hereineffective to reduce symptoms associated with plaque, gingivitis or gumdisease.

Table 1 below describes mouthwash compositions according to the aspectsdescribed herein.

TABLE 1 Example A Example B Example C Example D Example E Example FExample G Example H Ingredients (% w/w) (% w/w) (% w/w) (% w/w) (% w/w)(% w/w) (% w/w) (% w/w) Menthol 0.048 0.048 0.048 0.048 0.048 0.0480.048 0.048 Methyl salicylate 0.042 0.042 0.042 0.042 0.042 0.042 0.0420.042 Thymol 0.059 0.059 0.059 0.059 0.059 0.059 0.059 0.059 Eucalyptol0.089 0.089 0.089 0.089 0.089 0.089 0.089 0.089 Flavor 0.012 0.012 0.0120.012 0.012 0.012 0.012 0.012 Poloxamer 407¹ 0.100 0.150 0.200 0.2250.300 0.100 0.150 0.200 Kolliphor ® RH 40² — — — — — — — — Sugar esterL-1695³ 0.100 0.150 0.200 0.075 0.100 — — — Habo Monoester P90⁴ — — — —— 0.100 0.150 0.200 Habo Monoester L90⁵ — — — — — — — — SunSoft Q-12S⁶ —— — — — — — — Benzoic acid 0.070 0.070 0.070 0.070 0.070 0.070 0.0700.070 Sodium benzoate 0.080 0.080 0.080 0.080 0.080 0.080 0.080 0.080Sorbitol 14 14 14 14 14 14 14 14 Propylene glycol 7 7 7 7 7 7 7 7 WaterQ.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Total 100 100 100 100 100 100 100 100Turbidity (NTU) 12.51 3.49 2.37 10.61 4.09 12.17 6.84 2.78 Example IExample J Example K Example L Example M Example N Example O Example PIngredients (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (%w/w) Menthol 0.048 0.048 0.048 0.048 0.048 0.048 0.048 0.048 Methylsalicylate 0.042 0.042 0.042 0.042 0.042 0.042 0.042 0.042 Thymol 0.0590.059 0.059 0.059 0.059 0.059 0.059 0.059 Eucalyptol 0.089 0.089 0.0890.089 0.089 0.089 0.089 0.089 Flavor 0.012 0.012 0.012 0.012 0.012 0.0120.012 0.012 Poloxamer 407¹ — — — — — 0.050 0.075 0.100 Kolliphor ® RH40² 0.150 0.200 0.300 0.225 0.300 — — — Sugar ester L-1695³ 0.150 0.2000.100 — — — — — Habo Monoester P90⁴ — — — 0.075 0.100 — — — HaboMonoester L90⁵ — — — — — 0.150 0.225 0.300 SunSoft Q-12S⁶ — — — — — — —— Benzoic acid 0.070 0.070 0.070 0.070 0.070 0.070 0.070 0.070 Sodiumbenzoate 0.080 0.080 0.080 0.080 0.080 0.080 0.080 0.080 Sorbitol 14 1414 14 14 14 14 14 Propylene glycol 7 7 7 7 7 7 7 7 Water Q.S Q.S Q.S Q.SQ.S Q.S Q.S Q.S Total 100 100 100 100 100 100 100 100 Turbidity (NTU)3.94 2.57 3.77 6.97 8.69 3.99 1.15 0.73 Example Q Example R Example SExample T Example U Example V Example W Example X Ingredients (% w/w) (%w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) (% w/w) Menthol 0.048 0.0480.048 0.048 0.048 0.048 0.048 0.048 Methyl salicylate 0.042 0.042 0.0420.042 0.042 0.042 0.042 0.042 Thymol 0.059 0.059 0.059 0.059 0.059 0.0590.059 0.059 Eucalyptol 0.089 0.089 0.089 0.089 0.089 0.089 0.089 0.089Flavor 0.012 0.012 0.012 0.012 0.012 0.012 0.012 0.012 Poloxamer 407¹0.100 0.150 0.200 0.225 0.300 — — 0.075 Kolliphor ® RH 40² — — — — —0.100 0.300 — Sugar ester L-1695³ — — — — — — — — Habo Monoester P90⁴ —— — — — — — — Habo Monoester L90⁵ 0.100 0.150 0.200 0.075 0.100 0.3000.100 — SunSoft Q-12S⁶ — — — — — — — 0.225 Benzoic acid 0.070 0.0700.070 0.070 0.070 0.070 0.070 0.070 Sodium benzoate 0.080 0.080 0.0800.080 0.080 0.080 0.080 0.080 Sorbitol 14 14 14 14 14 14 14 14 Propyleneglycol 7 7 7 7 7 7 7 7 Water Q.S Q.S Q.S Q.S Q.S Q.S Q.S Q.S Total 100100 100 100 100 100 100 100 Turbidity (NTU) 6.11 2.90 2.10 10.78 3.381.70 8.70 13.62 Comparative Comparative Comparative ComparativeComparative Comparative Example Y Example Z Example CA Example CBExample CC Example CD Example CE Example CF Ingredients (% w/w) (% w/w)(% w/w) (% w/w) (% w/w) (% w/w) (% w/w (% w/w) Menthol 0.048 0.048 0.0480.048 0.048 0.048 0.048 0.048 Methyl salicylate 0.042 0.042 0.042 0.0420.042 0.042 0.042 0.042 Thymol 0.059 0.059 0.059 0.059 0.059 0.059 0.0590.059 Eucalyptol 0.089 0.089 0.089 0.089 0.089 0.089 0.089 0.089 Flavor0.012 0.012 0.012 0.012 0.012 0.012 0.012 0.012 Poloxamer 407¹ 0.1000.200 0.400 — — — — — Kolliphor ® RH 40² — — — 0.400 — — — — Sugar esterL-1695³ — — — — 0.400 — — — Habo Monoester P90⁴ — — — — — 0.400 — — HaboMonoester L90⁵ — — — — — — 0.400 — SunSoft Q-12S⁶ 0.300 0.200 — — — — —0.400 Benzoic acid 0.070 0.070 0.070 0.070 0.070 0.070 0.070 0.070Sodium benzoate 0.080 0.080 0.080 0.080 0.080 0.080 0.080 0.080 Sorbitol14 14 14 14 14 14 14 14 Propylene glycol 7 7 7 7 7 7 7 7 Water Q.S Q.SQ.S Q.S Q.S Q.S Q.S Q.S Total 100 100 100 100 100 100 100 100 Turbidity(NTU) 8.17 9.90 47.58 77 303 145 196 447 ¹Sigma aidrich. ²Cremophor ®RH40, BASF. ³Sucrose laurate, Mitsubishi-Chemical Foods Corporation.⁴Sucrose monopalmitate, Compass foods. ⁵Sucrose monolaurate, Compassfoods. ⁶Monolauric acid decaglycerin ester, Taiyo Kagaku Co., Ltd.

The present invention is best illustrated but is not limited to thefollowing examples.

EXAMPLES Example 1: Solubility of the Bioactive Component ofCompositions According to Some Aspects Presented Herein

The turbidity of the compositions described in Table 1 was measuredusing a portable turbidity meter (Hanna instruments, Woonsocket, RI,HI93703). Table 1 reports the turbidity measured in NephelometricTurbidity Units (NTU).

Referring to Table 1, the use ofpoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymersalone resulted in non-transparent formulations (i.e., a NTU ranging from20 to 100). In contrast, the use of a combination of apoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymer,and a polyol ester resulted in transparent compositions (i.e., a NTU ofless than 20, alternatively less than 10). These data suggest that thesolubilization capacity for the bioactive component was greatly enhancedby combining the poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene)block copolymer with the surfactant comprising a polyol ester or sugarester.

The ratio of the poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene)block copolymer to the surfactant comprising a polyol ester or sugarester appeared to affect the observed turbidity of the oral careformulations. Referring to Example V, a ratio of thepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymerto the surfactant comprising a polyol ester or sugar ester of 1:3appeared optimal.

Example 2: Antimicrobial Efficacy of Compositions According to SomeAspects Presented Herein

The antimicrobial efficacy of selected compositions described in Table 1was evaluated. Populations of Streptococcus mutans were contacted witheach formulation for 30 seconds. A commercially available alcohol-freemouthwash product (Listerine Zero®) was included as a positive control.Viable microorganisms were counted and data reported as a log reductioncompared to negative control (deionized water) in Table 2.

TABLE 2 Samples Log reduction Example A >4.81 Example B >4.81 ExampleC >4.81 Example D >4.81 Example E 4.12 Example F >4.81 Example G >4.81Example H 4.39 Example I >4.81 Example K 2.07 Example L 4.66 ExampleN >4.81 Example Q >4.81 Example R >4.81 Example S >4.81 Example T >4.81Example U 4.36 Example V >4.81 Example W 3.99 Example X >4.81 ExampleY >4.81 Example Z >4.81 Positive >4.81 control Negative 0 control

Referring to Table 2, the antimicrobial efficacy of most compositionswere comparable the positive control. Example E, H, K, L, W were lesseffective in inhibiting S. mutans compared to the positive control,which contain higher portions of Poloxamer 407 or Cremophor RH40,indicating the negative effect of Poloxamer 407 or Cremophor RH40 on theantimicrobial efficacy of bioactive oils. These data suggest that mostof the oral care compositions presented herein have an antimicrobialefficacy similar to commercial alcohol-free mouthwashes.

Example 3: Preparation of Compositions According to Some AspectsPresented Herein

Without intending to be limited to any particular theory, thecompositions described in Table 1 may be prepared by mixing thenon-ionic surfactant, aqueous phase (including orally acceptablesolvents and water-soluble components), and water-insoluble compounds,using any conventional mixing technology.

For example, one method may comprise (i) preparing a flavor concentratecomprising surfactants, oil (including menthol, methyl salicylate,thymol, eucalyptol, or other flavor compounds) and a solvent; and (ii)diluting the flavor concentrate into an aqueous phase.

In another example, the method may comprise (i) preparing a flavorconcentrate comprising a non-ionic surfactant comprising (i) asurfactant selected from the group consisting of polyol esters and sugaresters; a flavor component, such as, for example, oil (includingmenthol, methyl salicylate, thymol, eucalyptol, or other flavorcompounds); and at least one orally acceptable solvent, and (ii)diluting the flavor concentrate into an aqueous phase comprising asurfactant selected from the group consisting of:poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymers,poly(oxyethylene)-modified hydrogenated castor oils, andpoly(oxyethylene)-modified fatty acid monoesters of sorbitan.

Examples of flavor concentrates suitable for use according toembodiments described herein are disclosed in Table 3.

TABLE 3 Example a Example b Example c Example d Example e Example fExample g Example h Example i Example j Menthol, 21.74 21.74 17.24 33.3333.33 17.24 25.00 25.00 20.00 20.00 methyl salicylate, thymol,eucalyptol and other flavor Poloxamer 13.05 13.05 20.69 6.67 13.34 20.69407¹ Kolliphor ® 22.50 15.00 24.00 8.00 RH 40² Sugar ester 13.05 6.9015.00 8.00 L-1695³ Habo 13.05 7.50 Monoester P90⁴ Habo 20.00 13.33 6.9024.00 Monoester L90⁵ Propylene 39.13 39.13 41.38 40.00 40.00 41.38 45.0045.00 48.00 48.00 glycol Glycerol Ethy lactate Water 13.03 13.03 13.7913.79 Example k Example l Example m Example n Example o Example pExample q Example r Example s Example t Example u Menthol, 56.25 50.0043.75 37.50 50.00 43.75 37.50 56.25 50.00 43.75 37.50 methyl salicylate,thymol, eucalyptol and other flavor Habo 33.75 30.00 26.25 22.50 30.0026.25 22.50 33.75 30.00 26.25 22.50 Monoester L90¹ Propylene 2.50 5.007.50 10.00 glycol Glycerol 10.00 15.00 20.00 Ethyl lactate 10.00 20.0030.00 40.00 10.00 15.00 20.00 7.50 15.00 22.50 30.00 Example v Example wExample x Example y Example z Example aa Example ab Example ac Menthol,56.25 50.00 43.75 37.50 35.71 35.71 30.00 30.00 methyl salicylate,thymol, eucalyptol and other flavor Habo 33.75 30.00 26.25 22.50 21.4321.43 18.00 18.00 Monoester L90¹ Propylene 10.00 20.00 30.00 40.00 21.4332.14 39.00 26.00 glycol Glycerol 21.43 10.71 13.00 26.00 Example adExample ae Example af Example ah Example ai Example aj Example akExample al Example am Menthol, 50.00 43.75 37.50 50.00 43.75 37.50 50.0043.75 37.50 methyl salicylate, thymol, eucalyptol and other flavor Habo30.00 26.25 22.50 30.00 26.25 22.50 30.00 26.25 22.50 Monoester L90¹Propylene 10.00 15.00 20.00 6.67 10.00 13.33 5.00 7.50 10.00 glycolGlycerol 10.00 15.00 20.00 13.33 20.00 26.67 15.00 22.50 30.00 ¹Sigmaaldrich. ²Cremophor ®RH 40, BASF. ³Sucrose laurate, Mitsubishi-ChemicalFoods Corporation. ⁴Sucrose monopalmitate, Compass foods. ⁵Sucrosemonolaurate, Compass foods. ¹Sucrose monolaurate, Compass foods.

Publications cited throughout this document are hereby incorporated byreference in their entirety. Although the various aspects of theinvention have been illustrated above by reference to examples andpreferred embodiments, it will be appreciated that the scope of theinvention is defined not by the foregoing description but by thefollowing claims properly construed under principles of patent law.

1. An oral care composition comprising: a) a bioactive component in anamount from 0.01 to 10 wt % of the oral care composition; b) a non-ionicsurfactant comprising (i) a surfactant selected from the groupconsisting of: poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene)block copolymers, poly(oxyethylene)-modified hydrogenated castor oils,and poly(oxyethylene)-modified fatty acid monoesters of sorbitan, and(ii) a surfactant selected from the group consisting of polyol estersand sugar esters; c) at least one orally acceptable solvent; andoptionally, d) a C₂-C₄ monohydric alcohol, wherein a ratio of thesurfactant selected from the group consisting of:poly(oxyethylene)-poly(oxypropyl ene)-poly(oxyethylene) blockcopolymers, poly(oxyethylene)-modified hydrogenated castor oils, andpoly(oxyethylene)-modified fatty acid monoesters of sorbitan to thesurfactant selected from the group consisting of polyol esters and sugaresters is from 1:10 to 10:1; and wherein a ratio of the non-ionicsurfactant to the bioactive component is from 0.5 to
 3. 2. The oral carecomposition of claim 1, further comprising a flavor oil.
 3. The oralcare composition of claim 1, wherein an amount of the C₂-C₄ monohydricalcohol is from 0 to 10 wt % of the oral care composition.
 4. The oralcare composition of claim 1, wherein an amount of the C₂-C₄ monohydricalcohol is from 0 to 5 wt % of the oral care composition.
 5. The oralcare composition of claim 1, wherein the oral care composition does notcomprise the C₂-C₄ monohydric alcohol.
 6. The oral care composition ofclaim 1, wherein thepoly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymeris hydrophilic non-ionic surfactant sold under tradename Poloxamer 407,comprising a triblock copolymer consisting of a central hydrophobicblock of polypropylene glycol flanked by two hydrophilic blocks ofpolyethylene glycol (PEG).
 7. The oral care composition of claim 1,wherein the poly(oxyethylene)-modified fatty acid monoester of sorbitanis Tween
 80. 8. The oral care composition of claim 1, wherein thepoly(oxyethylene)-modified fatty acid monoester of sorbitan is Tween 20.9. The oral care composition of claim 1, wherein the sugar ester isselected from the group consisting of: sucrose laurate, sucrosemonolaurate, sucrose palmitate, sucrose monopalmitate, and combinationsthereof.
 10. The oral care composition of claim 1, wherein the sugarester is a sucrose ester.
 11. The oral care composition of claim 1,wherein the sugar ester is a fructose ester.
 12. The oral carecomposition of claim 1, wherein the polyol ester is a glycerol ester.13. The oral care composition of claim 1, wherein the polyol ester ismonolauric acid decaglycerin ester.
 14. The oral care composition ofclaim 1, wherein the ratio of the surfactant selected from the groupconsisting of: poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene)block copolymers, poly(oxyethylene)-modified hydrogenated castor oils,and poly(oxyethylene)-modified fatty acid monoesters of sorbitan to thesurfactant selected from the group consisting of polyol esters and sugaresters is from 1:5 to 5:1.
 15. The oral care composition of claim 1,wherein the ratio of the surfactant selected from the group consistingof: poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) blockcopolymers, poly(oxyethylene)-modified hydrogenated castor oils, andpoly(oxyethylene)-modified fatty acid monoesters of sorbitan to thesurfactant selected from the group consisting of polyol esters and sugaresters is from 1:3 to 3:1.
 16. The oral care composition of claim 1,wherein the orally acceptable solvent is selected from the groupconsisting of: water, polyol, sugar alcohols, a C₁₋₆ linear or branchedalkyl lactate, triacetine, triethylcitrate, benzylic alcohol, andcombinations thereof.
 17. The oral care composition of claim 16, whereinthe polyol is selected from the group consisting of: polyhydricalcohols, polyalkylene glycols, polyhydric alcohol esters, polyhydricalcohol ethers, and combinations thereof.
 18. The oral care compositionof claim 17, wherein the polyhydric alcohol is selected from the groupconsisting of: glycerol, butylene glycol, hexylene glycol,1,3-propanediol, propylene glycol, and combinations thereof.
 19. Theoral care composition of claim 18, wherein the polyhydric alcohol ispropylene glycol.
 20. The oral care composition of claim 17, wherein thepolyhydric alcohol ester and polyhydric alcohol ether are selected fromthe group consisting of: dipropylene glycol, ethoxydiglycol, andcombinations thereof.
 21. The oral care composition of claim 17, whereinthe polyalkylene glycol is selected from the group consisting of:polyethylene glycol, polypropylene glycol, and combinations thereof. 22.The oral care composition of claim 16, wherein the sugar alcohol isselected from the group consisting of: xylitol, sorbitol, mannitol,maltitol, inositol, allitol, altritol, dulcitol, galactitol, glucitol,hexitol, iditol, pentitol, ribitol, erythritol and mixtures thereof. 23.The oral care composition of claim 22, wherein the sugar alcohol isselected from the group consisting of sorbitol and xylitol or mixturesthereof.
 24. The oral care composition of claim 16, wherein the C₁₋₆linear or branched alkyl lactate is ethyl lactate.
 25. A method fortreating plaque, gingivitis or gum disease in a subject in need thereof,comprising the step of applying to tissues of the oral cavity of thesubject, an amount of the oral care composition of claim 1 effective toreduce symptoms associated with plaque, gingivitis or gum disease.